Effects of Physiotherapy Combined With Botulinum Neurotoxin in Patients With Cervical Dystonia With and Without an Effective Sensory Trick: Clinical and Functional MRI Findings
Trial Snapshot
- Phase
- Not Applicable
- Status
- Enrolling By Invitation
- Sponsor
- IRCCS San Raffaele
- Enrollment
- 49
- Locations
- 1
- Primary Endpoint
- Toronto Western Spasmodic Rating Scale (TWSTRS) score
Study Overview
Brief Summary
The primary aim of this study is to investigate improvements of dystonia severity in patients with cervical dystonia (CD) with (DYT-trick) and without sensory trick (DYT-no-trick) following 6 weeks of physiotherapy combined with botulinum toxin injection (BoNT).
The recruited patients will be divided into two groups according to the presence of an effective sensory trick (DYT trick and DYT no-trick groups).
The researchers analyzing clinical, neurophysiological and MRI data as well as the statistician will be blind about the allocation of subjects to the two groups. Considering the different clinical phenotypes of patients (DYT-trick and DYT-no-trick) clinical evaluators and physiotherapists cannot be blind.
All patients will perform the routinely BoNT injection and after 1 week they will start a multimodal physiotherapy program lasting 6 weeks, 3 times a week for 45 minutes each session. The physiotherapy treatment will include soft tissue mobilization of inoculated muscles, stretching exercises of the inoculated muscles, strengthening of antagonist muscles, and motor learning exercises (attentive strategies, feedback-based cervical active exercises). Exercises will be progressively difficult (increase of active range of motion -ROM) according to clinical improvements during the 6 weeks of treatment.
Clinical assessments will be performed at baseline (T0), after 6 weeks of treatment (W6) and before the next BoNT injection (about 12 weeks of follow-up, W12) to evaluate disease severity (TWSTRS), pain, active cervical range of motion, disability, quality of life and mood. Cervical movements during TWSTRS will be monitored using the Virtual Reality Rehabilitation System (VRRS), which includes the usage of magneto-inertial sensors to objectively assess joint positions and quality of movement. MRI evaluations will be performed at T0 and at W6 to investigate resting state functional Magnetic Resonance Imaging (fMRI) changes and fMRI changes of brain activation during the simulation and imagination of sensory trick.
SAI paradigm is obtained combing transcranial magnetic stimulation (TMS) with peripheral electrical stimulation techniques. It will be performed at baseline (before BoNT injection and physiotherapist training) and after week 6 of physiotherapist training.
A group of healthy subjects similar for age and sex to patients will be recruited to perform cognitive assessment and MRI at baseline.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Supportive Care
- Masking
- Single (Outcomes Assessor)
Masking Description
The statistician will be blind about the characteristics of the two groups. Considering the different clinical phenotypes of patients (DYT-trick and DYT-no-trick) clinical evaluators and physiotherapists cannot be blinded.
Eligibility Criteria
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •fo patients with Cervical Dystonia:
- •Adult onset idiopathic CD according to established diagnostic criteria (Albanese et al., Eur J Neur, 2011) with and without an effective sensory trick will be eligible for the study
Exclusion Criteria
- •for all participants
- •presence of fixed postures because of skeletal neck deformity;
- •history of (other) systemic, neurologic, psychiatric diseases, head injury, cardiovascular events, and cerebrovascular alterations visible at an MRI scan;
- •alcohol and/or psychotropic drugs abuse;
- •contraindication to perform MRI scan (cardiac pace-maker or other types of cardiac catheters, splinters or metallic shards, metallic prosthesis not compatible with magnetic field generated by MRI, claustrophobia).
Arms & Interventions
Patients with Cervical Dystonia and an effective sensory trick (DYT-trick)
Patients with an effective sensory trick will undergo a multimodal physiotherapy program for 6 weeks
Intervention: Multimodal physiotherapy program (Behavioral)
Patients with Cervical Dystonia and without an effective sensory trick (DYT-no-trick)
Patients without an effective sensory trick will undergo a multimodal physiotherapy program for 6 weeks
Intervention: Multimodal physiotherapy program (Behavioral)
Healthy subjects
Age- and sex-matched healthy subjects recruited to compare clinical and MRI characteristics at baseline.
Outcomes
Primary Outcomes
Toronto Western Spasmodic Rating Scale (TWSTRS) score
Time Frame: Baseline, after training (week 6) and 6 weeks after the end of training (week 12)
Rating scale measuring severity, disability and pain associated with cervical dystonia (score 0-85, higher score = worse condition)
Secondary Outcomes
- Beck Depression inventory (BDI) score(Baseline, after training (week 6) and 6 weeks after the end of training (week 12))
- Hamilton Anxiety Rating Scale (HAM-A) score(Baseline, after training (week 6) and 6 weeks after the end of training (week 12))
- Cervical range of motion(Baseline, after training (week 6) and 6 weeks after the end of training (week 12))
- Cervical Dystonia Impact Scale (CDIP-58) score(Baseline, after training (week 6) and 6 weeks after the end of training (week 12))
- Short-latency afferent inhibition (SAI) paradigm using transcranial magnetic stimulation (TMS)(Baseline, after training (week 6))
- Brain functional changes during functional magnetic resonance imaging (MRI) task(Baseline, after training (week 6))
- Brain functional changes during functional magnetic resonance imaging (MRI) "conventional" resting state(Baseline, after training (week 6))
- Brain functional changes during functional magnetic resonance imaging (MRI) "sensory trick" resting state(Baseline, after training (week 6))
Investigators
Prof. Massimo Filippi
MD
IRCCS San Raffaele